Roles for the Highwire/Wallenda Pathway in Regenerative and Degenerative Responses to Axonal Injury.

TL;DRAbstract

Axons allow neurons to communicate over long distances, and their long length makes them vulnerable to injury. Neurons make several important responses to axonal injury. One is that the axons that are still connected to the cell body can initiate new axonal growth. This requires transcriptional reprogramming, and an important question is how this nuclear event can be induced by an injury in a distal site of the axon. Another response is that the distal stump, which is disconnected from the cell body, degenerates through a process called Wallerian degeneration. This self-destruction process is poorly understood, but is misregulated in some neurodegenerative diseases. To study these responses in a model organism, I developed an axonal injury assay in Drosophila. I have characterized the function an axonal signaling pathway, which is regulated by the ubiquitin ligase Hiw, and its conserved axonal target, Wnd. I found that Hiw and Wnd, through a downstream signaling cascade, regulate sever

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